Abnormal vascular tone and reactivity of the limb blood supply is prominent in essential hypertension. While abnormalities of renal perfusion can clearly cause hypertension, little is known about renal vascular reactivity in these patients. Sodium restriction and drugs influencing sodium balance are widely used in treatment and have a profound influence on renal vascular tone and reactivity. Our working hypothesis in this study is that altered responsiveness of the renal blood supply to endogenous vasoconstrictor agents, norepinephrine and angiotensin, play a role in sustaining essential hypertension. Our major recent emphasis has been on the assessment of new pharmacologic agents which interrupt the renin-angiotensin system and thus provide a potentially powerful new tool for exploring angiotensin's contribution, as a complement to the measurement of the hormones. In the case of the sympathetic nervous system, agents which block the influence of norepinephrine on vascular smooth muscle have long been available, and our major recent emphasis has involved attempts to utilize the complimentary measurement of plasma hormone concentration to supplement the information from pharmacologic studies. Emphasis has also been given to the development of models which allow us to activate these systems reproducibly in man, either through emotioal or reflex pathways. Our ultimate objective is to define further the determinants of renal vascular tone and reactivity in normal man, the deviations from normal in patients with hypertension of varying etiology, and the relationship of these abnormalities to the state of the renin-angiotensin and sympathetic nervous systems.